Biology subjects

Login, H.

Publications and source records attributed to Login, H..

3 recordsLinked to original sources

bioRxiv2024

Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory

The claustrum complex is viewed as fundamental for higher order cognition; however, the circuit organization and function of its neuroanatomical subregions are not well understood. We demonstrated that some of the key roles of the CLA complex can be attributed to the connectivity and function of a small group of neurons in its ventral subregion, the endopiriform (EN). We identified a subpopulation of EN neurons by their projection to the ventral CA1 (ENvCA1-proj. neurons), embedded in recurrent circuits with other EN neurons and the piriform cortex. Although the ENvCA1-proj. neuron activity was biased toward novelty across stimulus categories, their chemogenetic inhibition selectively disrupted the memory-guided but not innate responses of mice to novelty. Based on our functional connectivity analysis, we suggest that ENvCA1-proj. neurons serve as an essential node for recognition memory through recurrent circuits mediating sustained attention to novelty, and through feed forward inhibition of distal vCA1 neurons shifting memory-guided behavior from familiarity to novelty.

neuroscience↗

bioRxiv2023

SorCS2 modulates neurovascular coupling via glutamatergic and calcium signaling in astrocytes

AO_SCPLOWBSTRACTC_SCPLOWSorCS2 is involved in trafficking of membrane receptors and transporters. SorCS2 is implicated in brain disorders, but the mechanism remains uncertain. We hypothesized that SorCS2 expression is important for neurovascular coupling. Brains from P8 and 2-month-old wild type mice were stained for SorCS2 and compared to SorCS2 knockouts (Sorcs2-/-). Changes in cerebral perfusion in response to sensory stimulation, i.e., neurovascular coupling, were compared in vivo. Neurovascular coupling was also assessed ex vivo in brain slices loaded with calcium-sensitive dye. Proteomics of astrocytes was analyzed for ingenuity pathways. SorCS2 was strongly expressed in astrocytic endfeet of P8 mice but only in few astrocytes from 2-month-old brains. Sorcs2-/- mice demonstrated reduced neurovascular coupling. This was associated with reduced astrocytic calcium response to neuronal excitation in Sorcs2-/- mice. No difference in cerebral artery caliber nor in endothelial function was seen between wild type and Sorcs2-/- mice. Proteomics indicated reduced glutamatergic signaling and suppressed calcium signaling in Sorcs2-/- astrocytes. We suggest that SorCS2 expression is important for neurovascular coupling due to modulation of glutamatergic and calcium signaling in astrocytes.

neuroscience↗

bioRxiv2023

SorCS2 binds progranulin and regulates motor axon outgrowth

Motor neuron development requires an orchestrated action of trophic factors and guidance cues for axons to reach their targets. Here, we identify SorCS2 as a novel receptor for progranulin (PGRN) that is required for motor axon outgrowth in zebrafish and mice. In both species motor neurons express SorCS2, and PGRN is produced in cells juxta-positioned the projecting axon, but in mice the neurons also co-express PGRN. In zebrafish, sorcs2 knockdown produces stunted and aberrantly branched motor axons, and in Sorcs2-/- mice, forelimb innervation and motor neuron regeneration are substantially perturbed; phenotypes also observed in fish and mice lacking PGRN. SorCS2 binds PGRN and while motor neuron cultures from wildtype mice respond to exogenous PGRN by axon outgrowth, knockout neurons are unresponsive. Remarkably, when co-expressed in the same cells, SorCS2 controls secretion of PGRN. We conclude that SorCS2 navigates motor neuron development and enables axon regeneration through binding of PGRN.

developmental biology↗